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离体哺乳动物心肌缺血时钾外流及动作电位缩短的机制

Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

作者信息

Gasser R N, Vaughan-Jones R D

机构信息

University Laboratory of Physiology, University of Oxford.

出版信息

J Physiol. 1990 Dec;431:713-41. doi: 10.1113/jphysiol.1990.sp018356.

Abstract
  1. Ischaemia was simulated in the isolated sheep cardiac Purkinje fibre and guinea-pig papillary muscle by immersing the preparations in paraffin oil. Ion-selective microelectrodes recorded potassium (Ks+) and pH (pHs) in the thin film of Tyrode solution trapped at the fibre surface while other microelectrodes recorded intracellular pH (pHi), membrane potential and action potentials (AP) (evoked by field stimulation), or membrane current (two-microelectrode voltage clamp in shortened Purkinje fibres). Twitch tension was also monitored. The paraffin oil model reproduced the salient characteristics of myocardial ischaemia, i.e. a decrease of twitch tension; a decrease of pHi and pHs; a rise in Ks+ (by 2-3 mM); a depolarization of diastolic membrane potential; considerable shortening of the AP (up to 30% within 4 min). 2. The sulphonylurea compounds, glibenclamide (200 microM) and tolbutamide (1 mM), known inhibitors of the KATP channel, completely blocked the ischaemic rise of Ks+ and prevented AP shortening. Ischaemic tension decline was notably less pronounced in the presence of sulphonylureas. 3. The ischaemic increase of slope conductance (Purkinje fibre) was prevented by 1 mM-tolbutamide and 200 microM-glibenclamide. 4. Sulphonylureas did not affect resting membrane potential, the AP or the current-voltage relationship under non-ischaemic conditions (this also indicates that ischaemic Ks+ accumulation is not fuelled by the background K+ current [iK1] which was shown, as expected, to be Ba2+ sensitive). 5. In a normally perfused preparation, reducing intracellular ATP by inhibiting glycolysis with 2-deoxyglucose (DOG) produced a similar AP shortening plus a membrane hyperpolarization, both of which were inhibited by tolbutamide or glibenclamide. The AP shortening was not related uniquely to the fall of pHi observed under these conditions since experimentally reducing pHi (by reducing pHo in the absence of DOG) lengthened rather than shortened the AP. 6. The possibility that the ischaemic rise in Ks+ might be the cause of AP shortening was excluded by the observation that, in a normally perfused Purkinje fibre, experimentally reducing pHi (by an amount similar to that seen during ischaemia) completely neutralized the AP-shortening effect of an elevated Ko+ (from 4.5 to 6.5 mM). Furthermore, the sulphonylurea-sensitive AP shortening seen during DOG treatment could not have been associated with a Ks+ rise since, in these particular experiments, the fibres were well perfused and diastolic membrane potential hyperpolarized.(ABSTRACT TRUNCATED AT 400 WORDS)
摘要
  1. 通过将分离的绵羊心脏浦肯野纤维和豚鼠乳头肌浸入石蜡油中来模拟缺血。离子选择性微电极记录被困在纤维表面的台氏液薄膜中的钾离子(Ks+)和pH值(pHs),而其他微电极记录细胞内pH值(pHi)、膜电位和动作电位(AP,由场刺激诱发)或膜电流(在缩短的浦肯野纤维中采用双微电极电压钳)。同时监测抽搐张力。石蜡油模型再现了心肌缺血的显著特征,即抽搐张力降低;pHi和pHs降低;Ks+升高(升高2 - 3 mM);舒张期膜电位去极化;动作电位显著缩短(4分钟内缩短达30%)。2. 磺酰脲类化合物,格列本脲(200 microM)和甲苯磺丁脲(1 mM),已知的KATP通道抑制剂,完全阻断了缺血时Ks+的升高并防止动作电位缩短。在存在磺酰脲类药物的情况下,缺血时张力下降明显不那么显著。3. 1 mM甲苯磺丁脲和200 microM格列本脲可防止缺血时斜率电导的增加(浦肯野纤维)。4. 磺酰脲类药物在非缺血条件下不影响静息膜电位、动作电位或电流 - 电压关系(这也表明缺血时Ks+的积累不是由背景钾电流[iK1]驱动的,如预期的那样,iK1对Ba2+敏感)。5. 在正常灌注的标本中,用2 - 脱氧葡萄糖(DOG)抑制糖酵解以降低细胞内ATP会产生类似的动作电位缩短以及膜超极化,这两者都被甲苯磺丁脲或格列本脲抑制。动作电位缩短并非唯一与这些条件下观察到的pHi下降有关,因为通过实验降低pHi(在不存在DOG的情况下降低pHo)会使动作电位延长而非缩短。6. 缺血时Ks+升高可能是动作电位缩短原因的可能性被以下观察结果排除:在正常灌注的浦肯野纤维中,通过实验降低pHi(降低幅度与缺血时相似)完全抵消了升高的钾离子浓度(从4.5 mM升高到6.5 mM)对动作电位缩短的影响。此外,DOG处理期间观察到的磺酰脲类药物敏感的动作电位缩短不可能与Ks+升高有关,因为在这些特定实验中,纤维灌注良好且舒张期膜电位超极化。(摘要截短至400字)

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本文引用的文献

1
3
Ionic currents during hypoxia in voltage-clamped cat ventricular muscle.
Circ Res. 1980 Oct;47(4):501-8. doi: 10.1161/01.res.47.4.501.
6
Extracellular K+ accumulation during myocardial ischemia in isolated rabbit heart.
Am J Physiol. 1982 Apr;242(4):H619-28. doi: 10.1152/ajpheart.1982.242.4.H619.
7
Observations on experimental myocardial ischaemia.
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